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基于慢病毒载体的单纯疱疹病毒 1 型(HSV-1)糖蛋白 B 疫苗可提供针对 HSV-1 和 HSV-2 生殖器感染的交叉保护。

A lentiviral vector-based, herpes simplex virus 1 (HSV-1) glycoprotein B vaccine affords cross-protection against HSV-1 and HSV-2 genital infections.

机构信息

Retrovirus Center and Virology Section, Department of Experimental Pathology, University of Pisa, Pisa, Italy.

出版信息

J Virol. 2012 Jun;86(12):6563-74. doi: 10.1128/JVI.00302-12. Epub 2012 Apr 4.

Abstract

Genital herpes is caused by herpes simplex virus 1 (HSV-1) and HSV-2, and its incidence is constantly increasing in the human population. Regardless of the clinical manifestation, HSV-1 and HSV-2 infections are highly transmissible to sexual partners and enhance susceptibility to other sexually transmitted infections. An effective vaccine is not yet available. Here, HSV-1 glycoprotein B (gB1) was delivered by a feline immunodeficiency virus (FIV) vector and tested against HSV-1 and HSV-2 vaginal challenges in C57BL/6 mice. The gB1 vaccine elicited cross-neutralizing antibodies and cell-mediated responses that protected 100 and 75% animals from HSV-1- and HSV-2-associated severe disease, respectively. Two of the eight fully protected vaccinees underwent subclinical HSV-2 infection, as demonstrated by deep immunosuppression and other analyses. Finally, vaccination prevented death in 83% of the animals challenged with a HSV-2 dose that killed 78 and 100% naive and mock-vaccinated controls, respectively. Since this FIV vector can accommodate two or more HSV immunogens, this vaccine has ample potential for improvement and may become a candidate for the development of a truly effective vaccine against genital herpes.

摘要

生殖器疱疹由单纯疱疹病毒 1(HSV-1)和 HSV-2 引起,其在人群中的发病率不断上升。无论临床表现如何,HSV-1 和 HSV-2 感染都极易传染给性伴侣,并增加对其他性传播感染的易感性。目前尚无有效的疫苗。在这里,我们通过猫免疫缺陷病毒(FIV)载体传递 HSV-1 糖蛋白 B(gB1),并在 C57BL/6 小鼠中针对 HSV-1 和 HSV-2 阴道挑战进行了测试。gB1 疫苗引发了交叉中和抗体和细胞介导的反应,分别使 100%和 75%的动物免受 HSV-1 和 HSV-2 相关的严重疾病的影响。在完全受保护的 8 只疫苗接种动物中有 2 只发生了亚临床 HSV-2 感染,这通过深度免疫抑制和其他分析得到了证明。最后,接种疫苗使 83%的动物免受 HSV-2 剂量的攻击,而未经处理和未接种疫苗的对照组的死亡率分别为 78%和 100%。由于这种 FIV 载体可以容纳两种或更多的 HSV 免疫原,因此这种疫苗具有很大的改进潜力,可能成为开发真正有效的生殖器疱疹疫苗的候选疫苗。

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